Cryoglobulinemia and hepatitis C virus

The review presents recent data on cryoglobulinemiaassociated with a hepatitis C virus: prevalence, pathogenesis, clinical manifestations, laboratory diagnostics, approaches to therapy

PHARMACOECONOMIC ASSESSMENT OF USING INTERFERON-FREE REGIMENS FOR CHRONIC HEPATITIS C AFTER LIVER TRANSPLANTATION

This article contains analysis of current combination treatment regimens for chronic hepatitis C after liver transplantation. Antiviral therapy with long-acting interferons and ribavirin is of low efficiency and high costs. The clinical and economic benefits of interferon-free treatment regimen for patients infected with genotype 1 HCV using dasabuvir, paritaprevir boosted with ritonavir, ombitasvir (Viekira Pak) and ribavirin have been shown. Registration and introduction into clinical practice of new direct-acting antiviral drugs will significantly expand the arsenal of tools for the treatment of recurrent HCV infections, in particular in patients infected with hepatitis C virus genotypes 2 and 3

ФАРМАКОЭКОНОМИЧЕСКОЕ ОБОСНОВАНИЕ ИСПОЛЬЗОВАНИЯ БЕЗИНТЕРФЕРОНОВЫХ ТЕРАПЕВТИЧЕСКИХ СХЕМ ПРИ ХРОНИЧЕСКОМ ГЕПАТИТЕ С ПОСЛЕ ТРАНСПЛАНТАЦИИ ПЕЧЕНИ

This article contains analysis of current combination treatment regimens for chronic hepatitis C after liver transplantation. Antiviral therapy with long-acting interferons and ribavirin is of low efficiency and high costs. The clinical and economic benefits of interferon-free treatment regimen for patients infected with genotype 1 HCV using dasabuvir, paritaprevir boosted with ritonavir, ombitasvir (Viekira Pak) and ribavirin have been shown. Registration and introduction into clinical practice of new direct-acting antiviral drugs will significantly expand the arsenal of tools for the treatment of recurrent HCV infections, in particular in patients infected with hepatitis C virus genotypes 2 and 3. В статье проведен анализ существующих схем комбинированной противовирусной терапии хронического гепатита С после трансплантации печени. Проведение противовирусной терапии с использованием пролонгированных интерферонов и рибавирина низкоэффективно и высокозатратно. Доказано клиническое и экономическое преимущество безинтерферонового режима лечения пациентов, инфицированных вирусом гепатита С 1-го генотипа, с использованием дасабувира, паритапревира, бустированного ритонавиром, омбитасвира (Викейра Пак) и рибавирина. Регистрация и внедрение в клиническую практику новых препаратов прямого противовирусного действия позволит существенно расширить арсенал средств для лечения возвратной HCV-инфекции, в том числе у пациентов, инфицированным вирусом гепатита С 2-го и 3-го генотипа

Content of certain cytokines and chemokines in blood ofpatients with chronic hepatitis B in the early stages of liver fibrosis

Hepatitis B is an infectious viral disease in which damage or destruction of liver tissue occurs, and which can turn into a chronic form. In chronic hepatitis B (CHB), hepatocytes are replaced by connective tissue as they die, resulting in fibrosis, and then cirrhosis of the liver. Early diagnosis of liver fibrosis is an urgent task in the development of CHB. Already at this stage of the disease, the immune system is activated, which plays a leading role in liver damage in CHB. The main regulators of immune processes are cytokines, which mediate intercellular interactions. A separate group of cytokines are chemokines — proteins of cell migration. In CHB, they are responsible for infiltration of liver tissue by activated white blood cells. Cytokines and chemokines are active participants in fibrogenesis, so they can serve as biomarkers for the development of liver fibrosis, including in the early stages. The purpose of this study was to analyze the content of certain cytokines/chemokines in the peripheral blood of patients with CHB in order to search for potential biomarkers of the initial stages of liver fibrosis. The study included 30 patients with a confirmed diagnosis of CHB with stages of liver fibrosis F0-F1 on the Metavir scale, 36 patients with a diagnosis of chronic hepatitis C (F0-F1) and 37 conditionally healthy individuals as a control group. Concentrations of the following cytokines/chemokines were determined: IFNγ, TNFα, CCL2/MCP-1, CCL8/MCP-2, CCL20/MIP-3α, CXCL9/MIG, CXCL10/IP-10, CXCL11/I-TAC by multiplex analysis using xMAP technology (Luminex, USA). As a result of the study, it was found that in patients with CHB, the plasma content of cytokine TNFα and chemokines CCL2/MCP-1, CXCL9/MIG and CXCL10/IP-10 was increased, and the chemokine CCL8/MCP-2 was reduced, which indicates the possibility of using these cytokines/chemokines as biomarkers of liver damage in CHB. In the examined group of patients with CHB, there was no dependence of the concentrations of cytokines and chemokines in the blood plasma on the viral load, which may be explained by its low level. For plasma cytokines in patients with CHB, correlations were found between TNFα and CCL2/MCP-1 and CCL8/MCP-2 chemokines , which was not observed in the control group. At the same time, in the control group, a correlation was found between the content of TNFα and the chemokine CXCL9/MIG, which was not detected in the group of patients. For both groups, a correlation was found between the content of CXCL9/MIG and CXCL10/IP-10 chemokines. Based on the study data, an algorithm has been developed that allows us to establish chronic hepatitis B or chronic hepatitis C as the cause of the initial form of fibrosis F0-F1 in terms of the content of cytokines IFNγ, CCL2/MCP-1 and CCL8/MCP-2 in blood plasma with a diagnostic efficiency of 89.4%

Clinical and immunological characteristics of patients with chronic hepatitis C during antiviral therapy in interferon-free regimen

Aim. To study the biomarkers of liver inflammation that occur during antiviral therapy in the interferon-free regimen. Methods. 14 patients were examined during antiviral therapy of chronic viral hepatitis C genotype 1. Treatment with dasabuvir, ombitasvir, paritaprevir and ritonavir for 12 weeks was received by 8 patients. Daklatasvir and asunaprevir was administered to 6 patients for 24 weeks. 11 patients had the concentrations of cytokines/chemokines (TNFα, CCL2/MCP-1, CCL20/MIP-3α, CXCL9/MIG, CXCL10/IP-10, CXCL11/ITAC) measured in the blood plasma by multiplex analysis. In six patients, the content of CXCR3+ and CCR6+ receptors in different subpopulations of lymphocytes was determined by flow cytofluorimetry. Patients were divided into 2 groups: without liver fibrosis and with severe fibrosis. Results. 100% demonstrated virologic response. In both groups, significant reduction of CXCL10/IP-10 concentration was found in the patients at the end of treatment compared to pre-therapy (p=0.025 and 0.00015, respectively). In the first group a tendency to increase of the relative content of T-lymphocytes (p=0.065) was observed, and in the second group, a significant increase of the relative content of TNKCCR6+ (p=0.02) was observed. Conclusion. Chemokine CXCL10/IP-10 is a biomarker characterizing the decrease of liver inflammation during therapy and not depending on the degree of liver fibrosis. The tendency to increase of the relative content of T lymphocytes in the first group and a significant increase in TNKCCR6+ cells during treatment in the second group may play an important role in eliminating hepatitis C virus

ЛЕТАЛЬНЫЕ ИСХОДЫ ПРИ ГРИППЕ: КЛИНИКО-МОРФОЛОГИЧЕСКИЙ ПОДХОД К НЕПОСРЕДСТВЕННЫМ ПРИЧИНАМ СМЕРТИ

Influenza is one of the most outspread infections not seldom leading to lethal outcomes. Immediate death causes are analyzed rarely. Material and methods. We provided clinic-pathological correlations in 23 cases with lethal outcomes in 1999, 15 – in 2009, 31 in 2016 and 10 in 2017. Results. It was shown that in 2009 and 2017 most frequent lethal outcomes were related to bacterial superinfection in elderly people with severe background pathology. In 2009 and 2016 the leading role played respiratory distress syndrome predominantly in people of middle age, frequently with obesity. Conclusions: by circulation of different strains of influenza A virus the disease has substantial peculiarities. Lethal outcomes may be related: 1) severe respiratory insufficiency due to respiratory distress syndrome; 2) generalized viral infection; 3) secondary bacterial pneumonia; 4) aggravation of severe somatic diseases. Many aspects of pathogenesis need complex.study.Грипп является одной из самых распространенных инфекций, приводящих к нередким летальным исходам. Непосредственные причины смерти при гриппе анализируются редко.Материал и методы: проведены клинико-морфологические сопоставления в 23 наблюдениях с летальным исходом взрослых в 1999 г., 15 – в 2009 г., 31 – в 2016 г. и 10 – в 2017 г.Результаты: показано, что в 2009 и 2017 гг. наиболее часто летальные исходы были связаны с бактериальной суперинфекцией, как правило, у пожилых людей с тяжелой фоновой патологией. В 2009 и 2016 гг. ведущую роль играл респираторный дисстресс-синдром преимущественно у лиц среднего возраста, чаще с ожирением.Выводы: при циркуляции разных штаммов вируса гриппа типа А заболевание имеет существенные особенности. Летальные исходы могут быть связаны с: 1) тяжелой дыхательной недостаточностью при респираторном дисстресс-синдроме; 2) генерализованной вирусной инфекцией; 3) вторичной бактериальной пневмонией; 4) обострением тяжелых соматических заболеваний. Многие аспекты патогенеза нуждаются в комплексном изучении.

ЭПИДЕМИОЛОГИЧЕСКИЕ И КЛИНИКО-ЛАБОРАТОРНЫЕ ОСОБЕННОСТИ ТЕЧЕНИЯ ЗАВОЗНЫХ СЛУЧАЕВ МАЛЯРИИ НА ТЕРРИТОРИИ СЕВЕРО-ЗАПАДНОГО ФЕДЕРАЛЬНОГО ОКРУГА

Purpose: analysis of epidemiological, clinical and laboratory features of imported malaria in the North-Western Federal district (NWFD) in 2012–2016. Research materials: the study included 84 patients treated for malaria in the hospitals of the NWFD. Results: 84 cases of malaria were registered in the NWFD from 2012 to 2016, which constituted 18,9% of all cases registered inRussian Federation(n=445):St. Petersburg(n=60),Arkhangelsk(n=10),Murmansk(n=5),Leningradregion (n=4),Vologdaregion (n=2) and 1 case in Komi,NovgorodandKaliningradregion. Patients with malaria had a history of a recent visit to: Asian countries (37%, n=31), West Africa (35%, n=30), North Africa (11%, n=7),South Africa(8%, n=7), East and Central Africa (3% correspondingly),Dominican Republic,CubaandSouth America(1% correspondingly). Pl. vivax was most common cause of malaria in patients visited Asia (87%), while recent travel to West Africa predispose patients to malaria caused by Pl. vivax in 37%, Pl. falciparum in 57% and Pl. оvale in 6% of all cases. All patients arrived from the North, South, Central Africa andDominican Republichad malaria caused by Pl. falciparum. Conclusion: in NWFD in 2012-2016 in the process of providing care to patients with malaria the following trends were marked: late referral of patients for medical care, careless collection of epidemiological data and travel history, late diagnosis of the disease, insufficient supply of antimalarial drugs and severe malaria in patients with comorbidity. Lack of adequate therapy with modern drugs has led to the lethal cases in patients with tropical malaria and the occurrence of late relapses of tertian malaria.Цель: анализ эпидемиологических и клинико-лабораторных особенностей течения завозных случаев малярии на территории Северо-Западного федерального округа (СЗФО) в 2012–2016 гг. Материалы и методы: в исследование включено 84 пациента с малярией, наблюдавшихся в стационарах СЗФО. Результаты: с 2012 по 2016 г. в СЗФО зарегистрировано 84 случая малярии – 18,9% от всех случаев по РФ (n=445): в Санкт-Петербурге (n=60), Архангельской (n=10), Мурманской (n=5), Ленинградской (n=4), Вологодской области (n=2) и по 1 – в Коми, Новгородской и Калининградской области. Недавно прибыли из азиатских стран 37% (n=31), из Западной Африки – 35% (n=30), из Северной Африки – 11% (n=7), из Южной Африки – 8% (n=7), по 3% из Восточной и Центральной Африки и по 1% из Доминиканской Республики, Кубы и Южной Америки. У прибывших из Азии в основном выявлялся Pl. vivax (87%), а у посещавших страны Западной Африки Pl. vivax – у 37%, Pl. falciparum – у 57%, Pl. оvale – у 6%. У приехавших из Северной, Южной, Центральной Африки и Доминиканы выделен только Pl. falciparum. Заключение: в СЗФО в 2012–2016 гг. в процессе оказания помощи больным малярией были отмечены следующие тенденции: позднее обращение больных за медицинской помощью, недостаточно тщательный сбор эпидемиологического анамнеза и анамнеза путешествий, несвоевременная диагностика заболевания, недостаточная обеспеченность противомалярийными препаратами и тяжелое течение малярии у пациентов с коморбидностью. Невозможность проведения адекватной терапии современными препаратами привела к развитию летальных исходов от тропической малярии и возникновению поздних рецидивов трехдневной малярии

ЗАВОЗНОЙ СЛУЧАЙ ТРОПИЧЕСКОЙ МАЛЯРИИ С ЛЕТАЛЬНЫМ ИСХОДОМ В САНКТ-ПЕТЕРБУРГЕ

.

Отечественные и зарубежные исследования Анаферона детского: эффективность, безопасность и опыт применения (обзор литературы)

Interest in acute respiratory viral infections (ARVI) in children does not tend to decrease and is determined by their high prevalence, relatedness to «uncontrollable infections» in most cases and presence of age limits in the use of antiviral drugs. Presently, focus on the use of national drugs is made in the RF clinical practice. An innovative drug Anaferon for children was developed by the Russian pharmaceutical company OOO «NPF «Materia Medica Holding» and registered in Russia in 2002.The summary purpose is to classify and analyze national and international publications on the results of non-clinical and clinical investigation of Anaferon for children efficacy and safety in ARVI and other viral infections.Study method: exploratory and analytical.Results: the summary presents the data of non-clinical studies justifying the drug mechanism of action at molecular level ensuring its combined antiviral and immunomodulating efficacy. The results obtained in the experiment were verified by clinical studies and are reflected in numerous scientific publications including international ones. The summary contains analysis of the results of clinical studies of the drug in children with ARVI including influenza. Anaferon for children was found to reduce duration of the main clinical symptoms of ARVI and influenza, incidence of bacterial complications, it is well-tolerated and has high safety profile. The open-label randomized comparative study of Anaferon for children efficacy and safety vs. Oseltamivir in influenza demonstrated clinical efficacy of these drugs. Numerous publications evidence that Anaferon for children exerts antiviral effect against most viruses causing acute respiratory viral infections as well as herpes viruses, viruses causing intestinal infections and tick-borne encephalitis. The list of scientific publications on the drug consists of approximately 800 references including more than 50 articles in foreign languages, particularly in journals with high citation index.Интерес к проблеме острых респираторных вирусных инфекций (ОРВИ) у детей не снижается и определяется их широким распространением, принадлежностью в большинстве случаев к «неуправляемым инфекциям» и наличием возрастных ограничений в использовании противовирусных препаратов. В настоящее время в Российской Федерации делается акцент на использование в клинической практике лекарственных средств отечественного производства. Инновационным препаратом является Анаферон детский, разработанный российской фармацевтической компанией НПФ ООО «Материа Медика Холдинг» и зарегистрированный в России в 2002 г. Цель обзора – систематизировать и проанализировать отечественные и зарубежные публикации о результатах доклинического и клинического изучения эффективности и безопасности препарата Анаферон детский при ОРВИ, а также других вирусных инфекций.Метод исследования: поисково-аналитический.Результаты. В обзоре представлены данные доклинических исследований, которые обосновывают механизм действия препарата на молекулярном уровне, обеспечивающий его сочетанную противовирусную и иммуномодулирующую эффективность. Полученные в эксперименте результаты подтверждены клиническими исследованиями и отражены в многочисленных научных публикациях, включая зарубежные. В обзоре приведен анализ результатов клинических исследований использования препарата у детей при ОРВИ, включая грипп. Доказано, что Анаферон детский значительно снижает продолжительность основных клинических симптомов ОРВИ и гриппа, частоту бактериальных осложнений, хорошо переносится и имеет высокий профиль безопасности. Открытое рандомизированное сравнительное исследование эффективности и безопасности Анаферона детского при гриппе по сравнению с Осельтамивиром продемонстрировало клиническую эффективность указанных препаратов. Из многочисленных публикаций следует, что Анаферон детский проявляет противовирусное действие по отношению  не только к большинству вирусов, вызывающих острые респираторные вирусные инфекции, но и к вирусам герпеса, вирусам, вызывающим кишечные инфекции, вирусу клещевого энцефалита. Перечень научных публикаций по препарату составляет около 800 источников, включая более 50 публикаций на иностранных языках, в том числе в журналах с высоким индексом цитируемости

Clinical and epidemiological characteristics of male hypogonadism in type 2 diabetes in Russia: combined analysis of study data for the period 2005–2022

Background: Male hypogonadism is associated with type 2 diabetes mellitus (T2DM), therefore, it is of interest to study its clinical and epidemiological characteristics. These data are published, but their fragmentation and small sample sizes are a problem. A summary assessment of the combined primary data of the conducted studies will provide sufficient representativeness and will allow to extrapolate the results to the general Russian population with T2DM.Aim: Assessment of the clinical and epidemiological characteristics and aggravating factors of male hypogonadism in T2DM in Russia.Materials and methods: A Combining primary data (anamnesis, anthropometric indicators, laboratory tests) of full-design, cross-sectional, screening studies of hypogonadism in men with T2DM conducted on the territory of the Russian Federation in the period from 2005 to 2022. The groups were compared using the Mann-Whitney U-test for quantitative indicators and χ² with Yates’ correction for qualitative ones. Differences were considered statistically significant with p <0,05. The groups were compared using the Mann-Whitney U-test and χ² with Yates correction. Differences were considered statistically significant at p<0.05.Results: Hypogonadism was detected in 893 of 1576 men (56,7%) with T2DM. Patients with hypogonadism were statistically significantly older, had higher body mass index (BMI), worse glycemic control than eugonadal men. There was ­statistically significantly higher prevalence of macroangiopathies and polyneuropathy in hypogonadal patients.Conclusion: The prevalence of male hypogonadism in T2DM 56,7%. Its development is due to age, obesity, worse glycemic control. Hypogonadism syndrome is associated with the development of diabetic macroangiopathy and polyneuropathy. Severe violation of glycemic control (glycated hemoglobin (HbA1c) 10% or more) significantly reduces testosterone production and increases the prevalence of hypogonadism